The main objective of the proposed research is the development of chemical methods for selective modification and cleavage of proteins, and the use of such methods for gaining information regarding the structure and function of proteins and enzymes. Specific methods for chemical cleavage of proteins at cysteine and selected methionine residues that are of considerable potential utility in primary structure determination, will be developed and improved. The use of S-cyanylation as a specific probe for evaluating the type and extent of involvement of thiol groups in enzymic catalysis will be explored. The mode of action of enzymes which recognize or react with Beta-lactam drugs of the penicillin and the cephalosporin types will be studied, using methods of chemical modification. A similar approach will also be applied for studying protein-protein interactions in multi-protein complexes such as those formed by several proteinases and their protein inhibitors. We shall also extend our studies on the methodology of covalent chromatography by developing novel polymeric reagents for the specific covalent binding of peptides and proteins to insoluble carriers at selected amino acids. BIBLIOGRAPHIC REFERENCES: Arieh Gertler, Yuval Weiss and Yigal Burstein. Purification and characterization of procine elastase II and investigation of its elastolytic specificity. Biochemistry, 16, in press (1977). Yoram Shechter, Menachem Rubinstein and Abraham Patchornik. Selective covalent binding of methionyl-containing peptides and proteins to water insoluble polymeric reagents and their regeneration. Biochemistry, 16, 1424 (1977).